This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The successes and failures of various implicit solvent models in their applications to the biological problems arise in principle from their ability in maintaining the delicate balance of energetics between sets of competing interactions, i.e., the solvation preference of each sidechain and the peptide backbone in aqueous bulk solution versus the strength of solvent-mediated interactions between these moieties in a complex protein environment. To what extent a GB force field can capture this delicate balance appears to be a key in the success of its applications and both assessment of and improvement in the underlying theory are key objectives of this project.